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Solid Phase Synthesis of a Functionalized Bis-Peptide Using "Safety Catch" Methodology
Published on: May 15, 2012
Problem of aspartimide formation in Fmoc-based solid-phase peptide synthesis using Dmab group to protect side chain
Jarosław Ruczyński1, Brygida Lewandowska, Piotr Mucha
1Department of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland. jarecki@chem.univ.gda.pl
Abstract:
The sequence-dependent, acid- or base-catalysed aspartimide formation is one of the most serious side reactions in solid-phase synthesis of peptides containing aspartic acid. In the present work, we investigated the susceptibility of 4-(N-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl]amino)benzyl (Dmab), an aspartic acid beta-carboxy side-chain protecting group, for aspartimide formation. As a model, 15-amino acid-residue galanin fragment analogue containing the Asp-Ala motif was used during Fmoc-based solid-phase synthesis. Our study showed a strong tendency of Dmab-protected peptide to form aspartimide with unusual high efficiency. Furthermore, to investigate the susceptibility of Asp-Ala motif for aspartimide formation during the synthesis using Asp(ODmab), a 5-amino acid-residue galanin fragment LGPDA, different types of resin linkers, variety of Fmoc-deprotection conditions and coupling methods were applied.
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